Impurity profile study of lopinavir and validation of HPLC method for the determination of related substances in lopinavir drug substance.
Several related substances (RS4-RS10) were detected in lopinavir drug substance at levels ranging from 0.03% to 0.1% by employing gradient RP-HPLC. The related substances were identified by LC-MS analysis. These related substances were isolated and characterized by Mass, (1)H NMR and FT-IR spectral data. The separation was achieved on a YMC Pack ODS-AQ (250 mm x 4.6 mm, 5 microm) column thermostated at 45 degrees C using 0.02 M KH(2)PO(4) (pH 2.5): acetonitrile as a mobile phase in gradient elution mode. A PDA detector set at 210 nm was used for detection. The investigated validation elements showed the method has acceptable specificity, accuracy, linearity, precision, robustness and high sensitivity with detection limits and quantitation limits ranging from 0.028 microg/ml to 0.063 microg/ml and 0.084 microg/ml to 0.192 microg/ml respectively. The method can be used for routine quality control analysis and stability testing of lopinavir drug substance.
Chitturi
Sreenivasa Rao
SR
APL Research Centre (A Division of Aurobindo Pharma Limited), 313, Bachupally, Hyderabad 500072, Andhra Pradesh, India.
Bharathi
Ch
Ch
Reddy
A V Raghava
AV
Reddy
K Chandrasekhar
KC
Sharma
Hemant Kumar
HK
Handa
Vijay Kumar
VK
Dandala
Ramesh
R
Bindu
V Hima
VH
D002021:Buffers; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods; D004340:Drug Contamination; D004355:Drug Stability; D017408:Guidelines as Topic; D017320:HIV Protease Inhibitors / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D061466:Lopinavir; D013058:Mass Spectrometry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D004364:Pharmaceutical Preparations / Q000032:analysis / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry; D017680:Potassium Compounds / Q000737:chemistry; D011744:Pyrimidinones / Q000032:analysis / Q000138:chemical synthesis / Q000737:chemistry*; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry
D002021:Buffers; D017320:HIV Protease Inhibitors; D004364:Pharmaceutical Preparations; D010710:Phosphates; D017680:Potassium Compounds; D011744:Pyrimidinones; D014867:Water; D061466:Lopinavir; C013216:potassium phosphate